MC-ND-18
MC-ND-18 is an ATTEC degrader that degrades NLRP3 via the Autophagy pathway, with a DC50 of 125.5 nM in THP-1 cells. MC-ND-18 exhibits anti-inflammatory activity in a DSS-induced mouse model of colitis. MC-ND-18 can be used for research on inflammatory bowel disease. MC-ND-18 consists of an NLRP3 inhibitor (HY-156121), a linker (HY-W018745), and an LC3 ligand.
Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.
- CAS. Nr.: 3081572-53-1
- Formel: C42H42Br2IN3O9S
- Molecular Weight:1051.58
-
Speicherung:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Biologische Aktivität
-
Chemical Information
-
Lösungsmittel & Löslichkeit
- Protokoll
- Reinheit & Dokumentation
- Verweise
-
Help & FAQs
Biologische Aktivität
Beschreibung
IC50 & Target
[1]|
NLRP3 125.5 nM (DC50) |
In Vitro
MC-ND-18 (100-200 nM; 24 h) potently inhibits IL-1β secretion in PMA-differentiated THP-1 cells, with an inhibition rate of 73.6% at 200 nM and 45.8% at 100 nM[1].
MC-ND-18 (100-500 nM; 24 h) induces concentration-dependent degradation of NLRP3 in PMA-differentiated THP-1 cells, with degradation rates of 65% at 500 nM, 49% at 200 nM, and 13% at 100 nM[1].
MC-ND-18 (50 nM-1 μM; 24 h) induces NLRP3 degradation in PMA-differentiated THP-1 cells, with a DC50 of 125.5 nM, and the maximum degradation rate reaches up to 70% at 500 nM[1].
MC-ND-18 (50 nM-5 μM; 24 h) exhibits low cytotoxicity in PMA-differentiated THP-1 cells, and no significant reduction in relative cell viability is observed after incubation at concentrations ranging from 50 nM to 5 μM for 24 h[1].
MC-ND-18 (19.5 nM-5 μM) binds to purified NLRP3 protein lacking the LRR domain and LC3B protein, with Kd values of 0.929 μM and 3.548 μM, respectively, indicating that it exhibits concentration-dependent affinity for both targets[1].
MC-ND-18 (24 h) does not degrade NLRP3 in PMA-differentiated THP-1 cells via the proteasomal pathway, as combined treatment with the proteasome inhibitor MG132 does not attenuate its degrading activity[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:PMA-differentiated THP-1 cells
-
Concentration:100 nM, 200 nM
-
Incubation Time:24 h (co-incubation with LPS)
-
Result:Inhibited IL-1β secretion by 45.8 % at 100 nM.
Inhibited IL-1β secretion by 73.6 % at 200 nM.
-
Cell Line:PMA-differentiated THP-1 cells
-
Concentration:100 nM, 200 nM, 500 nM
-
Incubation Time:24 h (co-incubation with LPS)
-
Result:Degraded NLRP3 by 13 % at 100 nM.
Degraded NLRP3 by 49 % at 200 nM.
Degraded NLRP3 by 65 % at 500 nM.
-
Cell Line:PMA-differentiated THP-1 cells
-
Concentration:50 nM, 100 nM, 200 nM, 500 nM, 1000 nM
-
Incubation Time:24 h (co-incubation with LPS)
-
Result:Exhibited a concentration-dependent NLRP3 degradation profile from 50 nM to 500 nM.
Achieved a maximum degradation rate of 70 % at 500 nM.
Had a DC50 for NLRP3 degradation of 125.5 nM.
Showed reduced degradation efficiency at 1000 nM, consistent with a "hook effect" for bifunctional molecules.
-
Cell Line:THP-1 cells
-
Concentration:500 nM
-
Incubation Time:4 h
-
Result:Resulted in substantial colocalization of NLRP3 and LC3B, with a Pearson correlation coefficient of 0.53.
Parmacokinetics
In Vivo
MC-ND-18 (20 mg/kg; i.p.; daily) fails to alleviate DSS-induced colitis in NLRP3KO mice, confirming its therapeutic effects are dependent on the NLRP3 pathway[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:C57BL/6 (group size n=5 per cohort)[1]
-
Dosage:5 mg/kg; 20 mg/kg
-
Administration:i.p.; daily
-
Result:Reduced weight loss and dose-dependent suppression of DAI increase compared to the model group.
Mitigated colon shortening relative to the model group.
Markedly reduced intestinal mucosal damage, inflammatory cell infiltration, and loss of intestinal crypts compared to the model group.
Significantly reduced colonic NLRP3 and IL-1β protein levels compared to the model group.
-
Animal Model:C57BL/6-NLRP3KO (group size n=3 per cohort)[1]
-
Dosage:20 mg/kg
-
Administration:i.p.; daily
-
Result:Did not reduce body weight loss, suppress DAI increase, or mitigate colon shortening compared to the model group.
Showed no significant improvement in intestinal mucosal damage, inflammatory cell infiltration, or intestinal crypt loss compared to the model group.
Did not reduce colonic IL-1β levels compared to the model group; NLRP3 protein was undetectable in all cohorts.
Chemical Information
-
CAS. Nr. 3081572-53-1
-
Appearance Solid
-
Molecular Weight 1051.58
-
Formel C42H42Br2IN3O9S
-
Color Yellow to orange
-
SMILES
IC1=CC=C(C(/C(C2=O)=C/C3=CC(Br)=C(O)C(Br)=C3)=C1)N2CCOCCOCCOCCOC4=CC=C(S(NC(NC5=C6C(CCC6)=CC7=C5CCC7)=O)(=O)=O)C=C4
-
Versand
Room temperature in continental US; may vary elsewhere.
-
Speicherung
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Lösungsmittel & Löslichkeit
In Vitro:
DMSO : 100 mg/mL (95.09 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (2.38 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (2.38 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
-
-
-
-
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
-
%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
-
%+
-
+%Tween-80 + +
-
%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Reinheit & Dokumentation
-
Data Sheet (277 KB)
-
SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
-
Handling Instructions (2659 KB)
Verweise
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 0.9510 mL | 4.7548 mL | 9.5095 mL | 23.7738 mL |
| 5 mM | 0.1902 mL | 0.9510 mL | 1.9019 mL | 4.7548 mL | |
| 10 mM | 0.0951 mL | 0.4755 mL | 0.9510 mL | 2.3774 mL | |
| 15 mM | 0.0634 mL | 0.3170 mL | 0.6340 mL | 1.5849 mL | |
| 20 mM | 0.0475 mL | 0.2377 mL | 0.4755 mL | 1.1887 mL | |
| 25 mM | 0.0380 mL | 0.1902 mL | 0.3804 mL | 0.9510 mL | |
| 30 mM | 0.0317 mL | 0.1585 mL | 0.3170 mL | 0.7925 mL | |
| 40 mM | 0.0238 mL | 0.1189 mL | 0.2377 mL | 0.5943 mL | |
| 50 mM | 0.0190 mL | 0.0951 mL | 0.1902 mL | 0.4755 mL | |
| 60 mM | 0.0158 mL | 0.0792 mL | 0.1585 mL | 0.3962 mL | |
| 80 mM | 0.0119 mL | 0.0594 mL | 0.1189 mL | 0.2972 mL |
MC-ND-18 Related Classifications
HY-162588 Related Classifications
Powered by Bioz